tbuckley/cabot-search huggingface dataset:
Single cell multiomic profiling of high-grade serous carcinoma.
Authors: Leticia Assad Maia Sandoval, Mihai Dumbrava, Wazim Mohammed Ismail, Amelia Mazzone, Xiaonan Hou, Saravut John Weroha, Alexandre Gaspar-Maia
Journal: Journal of Clinical Oncology (2023)

e17535 Background: High-grade serous ovarian carcinoma (HGSOC) is the most frequent and deadliest type of ovarian cancer (OC). With the recent advances in transcriptomic and epigenomic profiling of cancer at single cell resolution, it has become clear that intra-tumor heterogeneity driven by genetic and epigenetic factors may be the basis of drug resistance. Current treatments are not homogeneously effective against all the cancer cell subpopulations, thus enabling resistance. With single cell sequencing technology, characterization of cell signatures and regulatory mechanisms may translate to prognostic markers and novel drug targets. Methods: The transcriptomic and epigenomic landscape of HGSOC was mapped for five tumor samples from debulking surgeries and one tissue patient-derived xenograft (PDX) using the 10X genomics sequencing platform. This strategy permits the combination of single cell ATAC-seq and single cell RNA-seq within the same nucleus (Multiome). Isolation of nuclei, library preparation and sequencing were performed following 10X genomics protocols. Sample quality and library quality were assessed by nuclear morphology and fragment size analysis, respectively. Sequenced reads were mapped to the human genome and downstream analysis including copy number variant prediction, pathway enrichment, motif enrichment and gene regulatory network analysis were performed. The sampled patients continue to be followed for clinical outcomes, such as response to therapy. Clinical data including patient age, grade, and stage of cancer, debulking status, CA-125 levels, and neoadjuvant status, were used in conjunction with the genomics data to characterize patient specific molecular regulatory signatures. Results: Cells from the six samples (total N= 26,421) were projected via UMAP. Immune and stromal cells were shown to cluster by cell-type while cancer cells clustered by patient. Cancer cells were identified as cycling cells, ciliated cells, cells with enrichment of the JAK-STAT signaling pathway, and cells exhibiting cancer stemness signatures. Transcription factor motifs and binding-site enrichment in open chromatin regions reveal transcription regulation-based subpopulations. Using the combined gene expression and open chromatin information from these cells, there is potential to uncover the genetic regulatory network(s) that drives treatment resistance. Conclusions: With single cell technology, specific clusters of cancer and tumor microenvironment cells can be classified. Beyond characterizing patient specific signatures, multiome enables the discovery of genomic, transcriptomic and epigenomic signatures that provide insight in tumor progression and treatment resistance.
Long-term efficacy and safety of pembrolizumab with R-CHOP as first-line therapy for DLBCL.
Authors: Carrie Ho, Jonathan R. Fromm, Min Fang, Brian G. Till, Mazyar Shadman, Andrew Cowan, Ryan C. Lynch, Vicky Wu, Jenna M. Voutsinas, Heather A. Rasmussen, Katharine Blue, Chaitra Shankar Ujjani, Andrei R. Shustov, Ryan Daniel Cassaday, Ajay K. Gopal, Stephen Douglas Smith
Journal: Journal of Clinical Oncology (2023)

7561 Background: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) represents the historical 1 st line treatment standard for DLBCL but fails to cure about 1/3 of patients. While generally ineffective in relapsed DLBCL-NOS, checkpoint inhibitors may have greater promise in untreated, immunocompetent patients. We previously reported safety and early efficacy of pembrolizumab plus RCHOP, noting objective responses in 90% of patients (CR 77%) and a 2-year progression-free survival (PFS) of 83%. We now report 5 year follow up of our study. Methods: Patients age &gt; 18 with untreated DLBCL or grade 3b follicular lymphoma, intended to receive 6 cycles of R-CHOP, were eligible. Pembrolizumab 200 mg IV with R-CHOP was given in 21-day cycles for 6 cycles. For this updated analysis, progression and survival events, and immune-related toxicities, are reported. Additionally, prognostic factors including tumor PD-L1 expression (Qualtek/Merck) were re-analyzed. Results: 30 patients were treated (13/30 with IPI 3-5). Median follow up is now 4.8 years (95% CI, 4.5-5.4). Since our initial report (Smith BJH 2019) we have observed 1 additional relapse (alive after CAR-T therapy) and 2 deaths in remission (1 urothelial carcinoma, 1 respiratory failure in the setting of progressive ILD). 5-year PFS is 71% (CI, 54-94%) and 5-year overall survival 83% (CI, 71-98%). During the study period and at long term follow up, there were 8 total immune-related adverse events (IRAEs) among 7 patients (23%) (Table). Four were treatment-emergent AE (occurred within 90 days of completing treatment): grade 1 hyperthyroidism, grade 2 hyperthyroidism, grade 3 pneumonitis, and grade 3 rash. There were 4 late IRAEs: colitis, paraneoplastic pemphigus, rheumatoid arthritis, and Graves’ disease, occurring at 3, 5, 8, and 46 months after completing treatment, respectively. PD-L1 tumor expression was documented in 19 of 23 (83%) tested patients. At long-term follow up, none of the 19 patients who had any PD-L1 expression have relapsed. Two out of the 4 patients with no PD-L1 expression have relapsed. On univariate analysis, PD-L1 H-score &gt;0 (p&lt;0.0001) was associated with improved PFS. Conclusions: At 5 year follow-up, pembrolizumab plus R-CHOP has led to durable responses in most patients with the best outcomes in PDL1-expressing disease. Furthermore, the safety profile was manageable, with a low rate of grade 3 or higher IRAEs (10%) and no consistent pattern of late events. These data support ongoing strategies incorporating PD-1/PDL-1 inhibitors in 1st line DLBCL therapy and confirmation of predictive biomarkers including tumor PD-L1 expression. Clinical trial information: NCT02541565 . [Table: see text]
Real-world clinical outcomes in patients (pts) with HR+/HER2- metastatic breast cancer (mBC) treated with chemotherapy (CT) in the United States (US).
Authors: Sara M. Tolaney, Kevin Punie, Allison W. Kurian, Ioanna Ntalla, Wendy Verret, Natalia Sadetsky, Nikoleta Sjekloca, Michael Stokes, Komal L. Jhaveri
Journal: Journal of Clinical Oncology (2023)

e18871 Background: HR+/HER2- mBC remains incurable, despite progress made with endocrine therapy (ET) + CDK4/6i in prolonging survival. After resistance to ET-based treatment, options are limited to CT and a decrease in survival is observed with every subsequent line of treatment received. This study describes real-world outcomes in pts with HR+/HER2- mBC initiating CT or previously treated with CT in the US. Methods: This retrospective, observational cohort study used the ConcertAI Patient360™ curated dataset of electronic medical record data from the US. Pts (≥18 years) diagnosed with HR+/HER2- mBC and initiating their first CT from January 2011 to June 2021 were included. Real-world outcomes were assessed for all pts who initiated treatment with a first CT, and those who were subsequently treated with a second, third, and fourth CT. Index date was defined as the CT start date of each systemic therapy line. Results: In total, 1545 pts met the eligibility criteria and were included for analysis. Pts were primarily female (99%) and White (76%); median age was 61 years (IQR, 52-69) and 68% had visceral metastases. Most pts (80%) were treated in a community setting and 41% received their first CT in 1L; 58% and 44% had prior exposure to ET and CDK4/6i in the mBC setting, respectively. The median time from mBC diagnosis to first CT was 12 months (IQR, 1.4-30.8). Among all pts included, 57%, 31% and 17% were subsequently treated with a second, third, and fourth CT, respectively, during the study period. Capecitabine and paclitaxel were the most used as the first (45% and 29%), second (35% and 30%), and third (25% and 22%) CT, while gemcitabine (22%) and eribulin (20%) were used most as fourth CT. Clinical outcomes assessed are summarized in the table. Median real-world overall survival (rwOS; 95% CI) from time of mBC diagnosis was 48.5 months (45.5-51.5). Median rwOS from first CT treatment start date was 23.3 months (21.3-25.4). In pretreated pts with 1, 2, or 3 prior lines of CT, median rwOS from each index date was 16.5 months (14.8-18.3), 11.8 months (10.4-13.1), and 9.1 months (7.3-11.2), respectively. Conclusions: Among pts with HR+/HER2- mBC in this analysis, CT choice and real-world clinical outcomes per systemic therapy line were comparable to existing literature. Outcomes decreased as pts advanced CT lines, indicating that in this setting the unmet need remains high. More efficacious treatment options are needed for ET-resistant, chemo-naïve pts and pts pretreated with CT with HR+/HER2- mBC. [Table: see text]
Update on the outcome of patients with metastatic prostate cancer in Kentucky: A Kentucky Cancer Registry (KCR) study.
Authors: Deepali Pandey, Quan Chen, Bin Huang, Zin Myint, Peng Wang
Journal: Journal of Clinical Oncology (2023)

e17121 Background: Overall survival (OS) of metastatic Prostate Cancer (mPC) in USA has improved by 3.6% during 2011–2016 compared to 2001–2005 (CDC, Oct 2020). Improvements in OS for mPC might reflect changes in clinical management, with approval of several new treatments. We aim to analyze if there is an improvement in OS of mPC in Kentucky between 2004-2011(T1) and 2012-2019(T2) and also analyze the impact of socioeconomic status as defined by Area Deprivation Index (ADI) on survival of mPC. Methods: All Kentucky male patients diagnosed between 2004 and 2019 who were &gt; 20 years old at diagnosis with first primary of metastatic prostate adenocarcinoma were extracted from the Kentucky Cancer Registry (KCR) data. Basic demographics and survival outcomes were compared between two time periods - T1 vs T2 and by Appalachian status. Kaplan Meir (KM) and Multivariate Cox Regression (MCR) were used to examine OS. ADI is divided into three groups – bottom tertile (low deprivation-ADI 1-3, Gr 1), middle tertile (ADI 4-6, Gr 2), and top tertile (high deprivation-ADI 7-10, Gr 3). Results: A total of 2619 patients with mPC were included in this retrospective analysis, of which 69.3% were Non-Appalachian (Non-AP) and 30.7% were Appalachian (AP). Caucasians predominated in both time periods (89.2% vs 90%). T2 had a higher proportion of patients aged 50-74 years (72.5% vs 64.2%), and private insurance (31.4% vs 27.1%) compared to T1. T1 had more patients who were &gt; 75 years (31.6% vs 24.8%), smokers (51.2% vs 47.4%), had medicare (59.6% vs 56.8%) and no insurance (4.2% vs 1.5%) compared to T2. KM showed improved OS in T2 (p &lt; 0.0001). Non-AP had better OS compared to AP and improved more between T1 &amp; T2. Median OS in months(95% CI) in T1 vs T2 for Non-AP was - 30(27-38) vs 58(53-69), p &lt; 0.0001 &amp; for AP was -34 (27-39) vs 44 (37-51), p = 0.0163. MCR showed that younger age, private insurance, being a nonsmoker, and receiving treatment, contributed to better OS. Gr 3 had higher proportion of African Americans (10.7% vs 6.5%), less private insurance (23.9% vs 39.7%) and more patients receiving no treatment (10.9% vs 7.5%) compared to Gr 1. AP Kentucky had more patients in Gr 3 (60.5% vs 39.5%) compared to Non-AP. KM showed OS had improved for all ADI groups in T2 vs T1. Within ADI groups, Gr 3 had significantly lower OS compared to Gr 1 &amp; Gr 2 (p = 0.04) in T2. In T1, OS was not different within ADI groups. In MCR, race and ADI did not impact OS. Conclusions: OS has improved in mPC patients in Kentucky during 2012-2019, likely due to new treatments being available. There is improvement in OS in Appalachian Kentucky but numerically lower than Non-Appalachian, and worse OS in Gr 3 during 2012-2019 which could be partially due to differences in access to new treatments (or quality of care). Interestingly, race did not impact survival.
Trends in cervical cancer incidence rates among demographic groups: A SEER database analysis.
Authors: Marisa Thierheimer, Akram Alkrekshi, Anas Al Zubaidi, Abdul Rahman Al Armashi
Journal: Journal of Clinical Oncology (2023)

e17524 Background: Cervical cancer (CC) is the fourth most common cancer in women worldwide, with most cases caused by human papillomavirus (HPV) infection. The incidence of CC has decreased since the mid-1900s due to effective cytological screening, treatment of precancerous lesions, and vaccinations against HPV. Nonetheless, over ten thousand women in the US are diagnosed with CC yearly. Up-to-date data on the trends in cervical cancer incidence rates (IR) among different racial and age groups is lacking. Here we present an in-depth analysis of these IR trends between 1975-2018. Methods: The National Cancer Institute SEER 9 database was used to generate CC IR from 1975 to 2018 as they relate to age, race, histopathology, and county classification. Joinpoint modeling was used to incidence trends and annual percent changes (APC) with 95% confidence intervals (CI) using Monte Carlo permutation analysis to generate best-fit models with a 2-tailed t-test (p&lt;0.05). Patients with CC were identified using ICD-O-3 primary site codes. Results: Overall, age-adjusted primary CC IR declined significantly between 1975 and 2018. Black individuals had the highest IR throughout the study period. When compared to the other racial groups, Black experienced a steeper decline in IR between 1975 and 2018. By 2018, the disparity in IR between Black individuals and White/Other individuals had nearly vanished. Of the two histopathologies studied, squamous cell carcinoma IR declined, while the IR of adenocarcinoma increased slightly. Among age groups, the IR among individuals aged 50-64 and 65+ decreased most dramatically over time. The two groups had the highest IR in 1975, but by 2018 the IR in both age groups had dropped below that of individuals aged 35-49 years. Patients in urban counties experienced similar IR decreases to those in urban and rural areas. Conclusions: Although screening and HPV vaccination initiatives have been successful at decreasing IR of CC, disparities in IR trends among racial and demographic groups persist. Examining age, racial, and community-specific CC IR trends at the population level will help prioritize resource allocation to reduce CC IR in all groups and minimize the existing gap. [Table: see text]
Disparity in regional recruitment across global cancer trials: A meta-analysis.
Authors: Noureen Asghar, Syed Arsalan Ahmed Naqvi, Arifa Bibi, Ahsan Ayaz, Kaneez Zahra Rubab Khakwani, Aishwarya Prasad, Umar Raza, Joseph Thirumalareddy, Mohsin Mirza, Narjust Florez, Sophia C. Kamran, Irbaz Bin Riaz
Journal: Journal of Clinical Oncology (2023)

6636 Background: Equitable regional enrollment in clinical trials is critical to addressing global inequities in health care outcomes. Therefore, we quantified disparities in regional recruitment in global cancer trials. Methods: Phase II/III clinical trials in prostate (PC), breast (BC), colorectal (CRC) and lung cancer (LC), and reporting regional recruitment were identified from Medline. Global regions were defined as North-(NA) and South- America (SA), Europe (EU), Africa (AF), Asia (AS), and Australia (AU). For multi-regional trials, enrollment incidence ratios (EIR) which compare region-wise trial enrollment against global estimates of region-wise specific cancer incidence obtained from Global Burden of Disease 2019 database. Trial-level EIRs were pooled using random-effects meta-analysis. A pooled EIR of &lt; 1.0 indicates underrepresentation of a particular region in clinical trial enrollment compared to the actual burden of the specific cancer in that region. Statistical analyses were conducted in R v4.1.2. Results: Of the total 2125 trials identified, 1681 (79.1%) trials with 691,800 participants reported information regarding regional recruitment. Among those, only 1400 (65.9%) trials reported proportions of patients from pre-defined regions. A total of 1231 (57.9%) trials were single-regional recruiting patients from EU (589; 47.8%), NA (329; 26.7%), AS (295; 23.9%), AU (10; 0.8%), AF (4; 0.3%), and SA (4; 0.3%). There was significant underrepresentation of patients from AS (EIR: 0.47; 95% CI: 0.41-0.54) in cancer clinical trials. This was consistent across different cancers: PC (0.49; 0.35-0.71), BC (0.63; 0.43-0.94), CRC (0.63; 0.43-0.94), LC (0.39; 0.30-0.50). Similarly, there is a trend of under-representation of patients from AF (0.67; 0.43-1.04). Consistently, patients from were under-represented in PC (0.43; 0.24-0.77) and LC (0.26; 0.09-0.79) trials. Patients from NA (1.27; 1.08-1.51), EU (1.64; 1.57-1.72), and AU (5.41; 3.90-7.51) were significantly over-represented in multi-regional cancer clinical trials. The results are provided in table. Conclusions: There is suboptimal reporting of region-wise enrollment in cancer clinical trials. Representation of Africa and Asia in cancer clinical trials appears to be less than their expected share based on their burden of cancer incidence. [Table: see text]
Different disease progression patterns based on RECIST and CA-125 criteria and the impact on prognosis in patients with ovarian cancer treated with PARP inhibitors.
Authors: Kun Song, Yana Ma, Hualei Bu, Yawen Zhang
Journal: Journal of Clinical Oncology (2023)

e17536 Background: We aimed to assess the clinical features of disease progression (PD) based on Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 criteria, and analyse the impact on prognosis in ovarian cancer patients treated with poly (ADP-ribose) polymerase (PARP) inhibitors. Methods: All epithelial ovarian cancer patients included in this retrospective analysis were admitted to the Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University between January 2011 and July 2021. All enrolled patients were treated with PARP inhibitor monotherapy or combination therapy with antiangiogenic agents and regularly assessed with RECIST and CA-125 criteria until disease progression confirmed by RECIST criteria. Patients were divided to RECIST PD group and CA-125 PD group based on regular assessment: RECIST PD group comprised patients who were first confirmed with RECIST-assessed PD and did not achieve PD according to CA-125 criteria during the subsequent 28 days; CA-125 PD group comprised as follows: (i) patients who were first diagnosed with RECIST-assessed PD and defined as consistent if CA-125 PD occurred within the following 28 days; (ii) patients who had doubled CA-125 levels for the first time, confirmed after at least 1 week, and defined as consistent if subsequent RECIST progression occurred within 28 days of the initial doubling of CA-125; (iii) patients in whom the first occurrence of CA-125 was doubled and confirmed after at least 1 week, defined as priority PD of CA-125 provided there was no progression in RECIST assessment during the subsequent 28 days. Results: A total of 124 patients were included, with 64 (51.6%) in RECIST PD group and 60 (48.4%) in CA-125 PD group. Forty-three patients (34.7%) had disease progression consistent with RECIST and CA-125 criteria, 64 patients (51.6%) had priority PD with RECIST criteria, and 17 patients (13.7%) had priority PD with CA-125 criteria. The median interval between disease progression as determined by priority CA-125 criteria and subsequent RECIST criteria was 55 days (range 29–192 days). Patients in CA-125 PD group had a higher proportion of lymph node progression (40.0% vs. 17.2%, p = 0.005), multi-site disease progression (41.7% vs. 21.9%, p=0.018), and a worse prognosis with a median overall survival (OS) of 70.5 vs. 87.2 months (hazard ratio (HR)=2.01, p=0.015). In multivariate analysis, residual lesions after primary surgery (no vs. yes, HR=0.493, p=0.015), duration of PARP inhibitor treatment (≤ 6 vs. &gt; 6 months, HR=2.262, p=0.006), priority criteria for PD (RECIST vs. CA-125, HR=0.441, p=0.006), and BRCA1/2 mutation status (wild-type vs. mutation, HR=2.150, p=0.028) were significantly associated with OS. Conclusions: Priority disease progression based on CA-125 criteria in ovarian cancer patients treated with PARP inhibitors might suggest a poor prognosis.
Associations of cancer history, food insecurity, and nonmedical financial worry and mortality risk in the US.
Authors: Zhiyuan Zheng, Jingxuan Zhao, Kewei Sylvia Shi, Xin Hu, Xuesong Han, Matthew P. Banegas, Robin Yabroff
Journal: Journal of Clinical Oncology (2023)

6537 Background: Cancer survivors often face substantial out-of-pocket medical costs, which can adversely affect their financial well-being. Cutting expenses on food and housing to save money are common coping strategies. However, little is known about the extent to which food insecurities and non-medical financial worries affect mortality risk after consideration of medical financial hardship. Methods: The 2013-2018 National Health Interview Survey (NHIS) and the NHIS linked mortality files with vital status through December 31, 2019 were used to identify cancer survivors (ages 18-64: n=5,110; ages 65-79: n=4,949) and individuals without a cancer history (ages 18-64: n=115,643; ages 65-79: n=24,785). Medical financial hardship included 3 domains: material, psychological, and behavioral. Food insecurity (e.g., worry about food running out) and non-medical financial worries (e.g., paying for monthly bills and housing) were separately summarized and categorized as severe, moderate, and minor/none levels. Using age as the time scale, associations of cancer history, food insecurity and non-medical financial worry and mortality risk were examined with weighted Cox proportional hazards models. Adjusted models included medical financial hardship, sex, educational attainment, marital status, health insurance, comorbid conditions, and survey year. All estimates accounted for complex survey design. Results: In our sample, about 13.8% (ages 18-64) and 7.9% (ages 65-79) reported moderate to severe levels of food insecurity, respectively; 32.1% (ages 18-64) and 19.2% (ages 65-79) reported moderate to severe levels of non-medical financial worries, respectively. In adjusted analyses, cancer survivors had increased mortality risk. After controlling for medical financial hardship, food insecurity was associated with higher mortality risk in both age groups, following a dose-response relationship (Table); Non-medical financial worry was associated with higher mortality risk in the 65-79 age group (Table). Conclusions: Standardized and comprehensive assessment of financial hardship and other social needs, such food insecurity, is essential to identify and mitigate adverse economic impacts of cancer. [Table: see text]